Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

Strategies for Implementing Machine Learning Algorithms in the Clinical Practice of Radiology.

Despite recent advancements in machine learning (ML) applications in health care, there have been few benefits and improvements to clinical medicine in the hospital setting. To facilitate clinical adaptation of methods in ML, this review proposes a standardized framework for the step-by-step implementation of artificial intelligence into the clinical practice of radiology that focuses on three key components: problem identification, stakeholder alignment, and pipeline integration. A review of the recent literature and empirical evidence in radiologic imaging applications justifies this approach and offers a discussion on structuring implementation efforts to help other hospital practices leverage ML to improve patient care. Clinical trial registration no. 04242667 © RSNA, 2024 Supplemental material is available for this article.

Quantification of abdominal fat from computed tomography using deep learning and its association with electronic health records in an academic biobank.

OBJECTIVE: The objective was to develop a fully automated algorithm for abdominal fat segmentation and to deploy this method at scale in an academic biobank. MATERIALS AND METHODS: We built a fully automated image curation and labeling technique using deep learning and distributive computing to identify subcutaneous and visceral abdominal fat compartments from 52,844 computed tomography scans in 13,502 patients in the Penn Medicine Biobank (PMBB). A classification network identified the inferior and superior borders of the abdomen, and a segmentation network differentiated visceral and subcutaneous fat. Following technical evaluation of our method, we conducted studies to validate known relationships with visceral and subcutaneous fat. RESULTS: When compared with 100 manually annotated cases, the classification network was on average within one 5-mm slice for both the superior (0.4 ± 1.1 slice) and inferior (0.4 ± 0.6 slice) borders. The segmentation network also demonstrated excellent performance with intraclass correlation coefficients of 1.00 (P < 2 × 10-16) for subcutaneous and 1.00 (P < 2 × 10-16) for visceral fat on 100 testing cases. We performed integrative analyses of abdominal fat with the phenome extracted from the electronic health record and found highly significant associations with diabetes mellitus, hypertension, and renal failure, among other phenotypes. CONCLUSIONS: This work presents a fully automated and highly accurate method for the quantification of abdominal fat that can be applied to routine clinical imaging studies to fuel translational scientific discovery.

WITHDRAWN: Radiology Extenders: Impact on Throughput and Accuracy for Routine Chest Radiographs.

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Zone- and layer-specific differences in proteoglycan content in patellofemoral pain syndrome are detectable on T1ρ MRI.

OBJECTIVE: Determine if differences in T1ρ would be detected in specific regions or layers of patellofemoral cartilage between patients with symptomatic patellofemoral pain syndrome and asymptomatic control subjects. MATERIALS AND METHODS: Ten subjects diagnosed with patellofemoral pain syndrome were compared with ten age-, gender-, and BMI-matched control subjects with no knee pain or prior trauma. Conventional turbo (fast) spin echo sequences and T1ρ-weighted imaging were performed on the symptomatic knee in each of the ten subjects. At the patella and distal femur, cartilage regions of interest were divided into medial and lateral sub-regions, each then further sub-divided by layer (superficial, middle, or deep). Two-tailed t test and chi-squared tests were used to analyze demographic data. A mixed effect model was run for each sub-region of T1ρ imaging. Statistical significance was determined using the likelihood ratio test against reduced models without patellofemoral pain syndrome symptomatic status as a fixed effect. RESULTS: There was no difference in age, sex, or BMI between symptomatic and control patients. T1ρ values were significantly higher among patellofemoral pain syndrome patients when compared with controls in the superficial zone of the lateral patella (58.43 vs. 50.83, p = 0.03) and the middle zone of the lateral patella (52.67 vs. 43.60, p = 0.03). T1ρ was also higher in the superficial zone of the medial femur (50.94 vs. 46.70, p = 0.09) with a value approaching statistical significance. CONCLUSION: We report statistically significant differences in the T1ρ value in the superficial and middle zones of the lateral patella in patients with patellofemoral pain syndrome who had no abnormalities seen on conventional MRI sequences, suggesting an alteration the macromolecular structure of the cartilage in this population.

Comparison of Study Activity Times for "Full" versus "Fast MRI" for Breast Cancer Screening.

PURPOSE: To optimize operations for a newly implemented abbreviated MR (AB-MR) breast cancer screening protocol, activity times were compared with the full-protocol examination. METHODS: Activity times from 70 AB-MR and 736 full MR screening studies were analyzed. Total study time was measured from opening to closing examinations and expected scan time by summing the time of acquisition for each imaging series for either protocol. Actual scan time was obtained from DICOM headers. Total technologist activity time was obtained by subtracting expected scan time from total study time. Technologist activity time included both scan-related and non-scan-related activities. RESULTS: The actual scan time for the AB protocol was 17.5 ± 0.5 min, compared with 28.8 ± 0.3 min (mean ± SE) for the full protocol (difference, 11.3 min; P < .0001). The total study time was 36.0 ± 3.2 min for AB-MRI and 49.7 ± 0.8 min for the full protocol (difference, 13.7 min; P < .0001), implying that the AB-MR protocol had only a 38% greater patient flow rate than the full protocol. CONCLUSIONS: The realized gains in patient flow rate were lower than expected based on scan times (65%) because of increased technologist activity time for the AB-MR protocol.

Reproducibility of 2D GluCEST in healthy human volunteers at 7 T.

PURPOSE: To investigate the reproducibility of gray and white matter glutamate contrast of a brain slice among a small group of healthy volunteers by using the 2D single-slice glutamate CEST (GluCEST) imaging technique. METHODS: Six healthy volunteers were scanned multiple times for within-day and between-day reproducibility. One more volunteer was scanned for within-day reproducibility at 7T MRI. Glutamate CEST contrast measurements were calculated for within subjects and among the subjects and the coefficient of variations are reported. RESULTS: The GluCEST measurements were highly reproducible in the gray and white matter area of the brain slice, whether it was within-day or between-day with a coefficient of variation of less than 5%. CONCLUSION: This preliminary study in a small group of healthy volunteers shows a high degree of reproducibility of GluCEST MRI in brain and holds promise for implementation in studying age-dependent changes in the brain.

In vivo GluCEST MRI: Reproducibility, background contribution and source of glutamate changes in the MPTP model of Parkinson's disease.

Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI is a recently developed technique to image glutamate. In the present study, we evaluated the reproducibility and background contamination to the GluCEST and source of the GluCEST changes in a mouse model of Parkinson's disease. Repeated measurements in five mice demonstrated an intra-animal coefficient of variation (CV) of GluCEST signal to be 2.3 ± 1.3% and inter-animal CV of GluCEST to be 3.3 ± 0.3%. Mice were treated with MPTP to create a localized striatal elevation of glutamate. We found an elevation in the GluCEST contrast of the striatum following MPTP treatment (Control: 23.3 ± 0.8%, n = 16; MPTP: 26.2 ± 0.8%, n = 19; p ≤ 0.001). Additionally, the positive association between glutamate concentration measured via 1H MRS and GluCEST signal was used to estimate background contribution to the measured GluCEST. The contribution of signal from non-glutamate sources was found to be ~28% of the total GluCEST. Immunohistochemical analysis of the brain showed co-localization of glutamate with GFAP in the striatum. This suggests that the elevated glutamate present in the striatum in this mouse model reflects astroglial proliferation or reactivity due to the action of MPTP. The potential of GluCEST as a biomarker for imaging inflammation mediated gliosis is discussed.

The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative Spine Changes, Low Back Pain, and Disability.

STUDY DESIGN: Cross-sectional. OBJECTIVE: To assess the distribution of the ultra-short time-to-echo (UTE) disc sign (UDS) and its association with disc degeneration, other magnetic resonance imaging (MRI) phenotypes, pain, and disability profiles. SUMMARY OF BACKGROUND DATA: Disc degeneration has been conventionally assessed by T2-weighted (T2W) signal intensity on MRI; however, its clinical utility has been questionable. UTE MRI assesses short T2 components. The authors have identified a new imaging biomarker on UTE-the UDS. METHODS: One hundred eight subjects were recruited. T2W MRI assessed disc degeneration and other phenotypes, and T1-rho MRI values represented quantitative proteoglycan disc profiles of L1-S1. UDS was detected on UTE (i.e., hyper-/hypointense disc band). A UDS score (cumulative number of UDS levels) and T2W summated lumbar degenerated scores (cumulative disc degeneration score) were assessed. Subject demographics, chronic low back pain (LBP), and disability profiles (Oswestry Disability Index: ODI) were obtained. RESULTS: UDS was noted in 39.8% subjects, 61.4% occurred at the lower lumbar spine and 39.5% had multilevel UDS. UDS subjects had significantly greater severity and extent of disc degeneration, and Modic changes (P < 0.05). By disc levels, a higher prevalence of disc degeneration/displacement, Modic changes, and spondylolisthesis were noted in UDS discs than non-UDS discs (P < 0.05). T1-rho values were also lower in UDS discs (P = 0.022). The majority of UDS could not be detected on T2W. The UDS score significantly correlated with worse ODI scores (r = 0.311; P = 0.001), whereas T2W cumulative disc degeneration score did not (r = 0.13; P = 0.19). LBP subjects exhibited more multilevel UDS (P < 0.015) but not on T2W MRI (P = 0.53). The UDS score was significantly related to LBP (P = 0.009), whereas T2W cumulative disc degeneration score was not (P = 0.127). CONCLUSION: This is the first study to report "UDS" in humans. UDS is a novel imaging biomarker that is highly associated with degenerative spine changes, chronic LBP, and disability than conventional T2W MRI. LEVEL OF EVIDENCE: 2.

Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological disorder and appears to have gender-specific symptoms. Studies have observed a higher frequency for development of PD in male than in female. In the current study, we evaluated the gender-based changes in cortical thickness and structural connectivity in PD patients. With informed consent, 64 PD (43 males and 21 females) patients, and 46 (12 males and 34 females) age-matched controls underwent clinical assessment including Mini-Mental State Examination (MMSE) and magnetic resonance imaging on a 1.5 Tesla clinical MR scanner. Whole brain high-resolution T1-weighted images were acquired from all subjects and used to measure cortical thickness and structural network connectivity. No significant difference in MMSE score was observed between male and female both in control and PD subjects. Male PD patients showed significantly reduced cortical thickness in multiple brain regions including frontal, parietal, temporal, and occipital lobes as compared with those in female PD patients. The graph theory-based network analysis depicted lower connection strengths, lower clustering coefficients, and altered network hubs in PD male than in PD female. Male-specific cortical thickness changes and altered connectivity in PD patients may derive from behavioral, physiological, environmental, and genetical differences between male and female, and may have significant implications in diagnosing and treating PD among genders.

T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease.

In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1ρ) imaging and CSF biomarkers (T-tau, P-tau and Aß-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1ρ images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1ρ maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1ρ values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1ρ and CSF biomarkers as variables was performed to classify each group. T1ρ was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1ρ and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1ρ predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1ρ and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1ρ predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1ρ were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1ρ showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1ρ and CSF biomarkers, between T1ρ and age, and between CSF biomarkers and age was observed. The combined use of T1ρ and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination.

Axial T1ρ MRI as a diagnostic imaging modality to quantify proteoglycan concentration in degenerative disc disease.

PURPOSE: The aim of the study was to investigate if axial T1ρ MR images had similar accuracy as established sagittal T1ρ MRI for the assessment of proteoglycan concentration and content in intervertebral degenerated discs (IDDs). METHODS: T1ρ and T2-weighted MR images of 12 intervertebral discs (IVDs) from 3 harvested human lumbar spines (levels L1-L2 to L5-S1) were grouped across their degenerative grade (Pfirrmann scores) and analyzed using a 3T MRI scanner in the axial and sagittal views. Post-processing of axial T1ρ-weighted images was performed using a Wiener filter. Median axial T1ρ values for traced regions of interest (ROIs) on color maps were compared against ROIs in the corresponding location in the sagittal plane of each disc. Assessment of sulfated glycosaminoglycans (GAGs) content was also performed. RESULTS: Comparison of post Wiener filtered mid-axial T1ρ values in the NP with corresponding mid-sagittal values revealed no statistical difference (P > 0.05). Higher axial T1ρ and biochemically measured GAGs content corresponded to a lower Pfirrmann grading of the IVDs. A strong association between the T1ρ values and the GAG contents was observed (r = 0.85, P = 0.0002). CONCLUSIONS: The axial T1ρ methodology was validated against sagittal T1ρ providing an augmented spatial representation of IVD and can facilitate localization of focal degeneration within IVDs. T1ρ values provided a better granularity assessment of degenerative disc disease as it correlated with proteoglycan concentration. Thus, Wiener filtering is an effective tool for removing noise from T1ρ-weighted axial MR images.

Early intervertebral disc degeneration changes in asymptomatic weightlifters assessed by t1ρ-magnetic resonance imaging.

STUDY DESIGN: Case-control study. OBJECTIVE: To evaluate early intervertebral disc degeneration quantified by T1ρ- and T2-weighted magnetic resonance imaging (MRI) in asymptomatic weightlifters compared with a healthy control group matched for sex and age. SUMMARY OF BACKGROUND DATA: Athletes consistently recruit or transfer high levels of repetitive forces through the spine, and MRI has documented a higher rate of intervertebral disc degeneration in athletes compared with matched controls. This study aims to analyze the potential role of T1ρ-MRI in the assessment of early degenerative changes occurring in intervertebral discs of young asymptomatic weightlifters compared with healthy controls. METHODS: Twenty-six asymptomatic young male weightlifters versus a sedentary control group matched for age and sex, both having no lower back pain nor any spinal symptoms, underwent MRI (1.5 T). Degenerative grade was assessed using T2-weighted images, according to the Pfirrmann scale. T1ρ mapping and values in the nucleus pulposus (n=130) were obtained. Differences in T1ρ value between among the groups and linear regression analyses with degenerative grade were determined. RESULTS: Pfirrmann degenerative grade did not show significant differences among groups. Instead, T1ρ values were significantly lower in the lumbar spine of weightlifters compared with controls (P<0.05). T1ρ values decreased linearly with degenerative grade. CONCLUSION: T1ρ values were significantly lower in athletes compared with a sedentary matched control group showing differences in intervertebral disc degeneration onset among individuals with lifestyle and environmental factors leading to back pain. T1ρ can be potentially used as a valid clinical tool to identify early changes in intervertebral disc on the verge of new emerging intervertebral discs regenerative strategies and treatments. LEVEL OF EVIDENCE: 4.

In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy.

Glutamate is the primary excitatory neurotransmitter in the brain, and is implicated in neurodegenerative diseases such as Alzheimer's disease (AD) and several other tauopathies. The current method for measuring glutamate in vivo is proton magnetic resonance spectroscopy ((1)H MRS), although it has poor spatial resolution and weak sensitivity to glutamate changes. In this study, we sought to measure the effect of tau pathology on glutamate levels throughout the brain of a mouse model of tauopathy using a novel magnetic resonance imaging (MRI) technique. We employed glutamate chemical exchange saturation transfer (GluCEST) imaging, which has been previously validated as a complimentary method for measuring glutamate levels with several important advantages over conventional (1)H MRS. We hypothesized that the regional changes in glutamate levels would correlate with histological measurements of pathology including pathological tau, synapse and neuron loss. Imaging and spectroscopy were carried out on tau transgenic mice with the P301S mutation (PS19, n=9) and their wild-type littermates (WT, n=8), followed by immunohistochemistry of their brain tissue. GluCEST imaging resolution allowed for sub-hippocampal analysis of glutamate. Glutamate was significantly decreased by 29% in the CA sub-region of the PS19 hippocampus, and by 15% in the thalamus, where synapse loss was also measured. Glutamate levels and synapse density remained high in the dentate gyrus sub-region of the hippocampus, where neurogenesis is known to occur. The further development of GluCEST imaging for preclinical applications will be valuable, as therapies are being tested in mouse models of tauopathy.

Novel imaging of the intervertebral disk and pain.

T-1-rho (T1ρ) magnetic resonance imaging (MRI) and disc height ratio (DHR) are potential biomarkers of degenerative disk disease (DDD) related to biochemical composition and morphology of the intervertebral disk (IVD), respectively. To objectively detect DDD at an early stage, the hypothesis was tested that the average T1ρ relaxation time of the nucleus pulposus (NP) correlates with the disk height of degenerate IVDs, measured by MRI. Studies were performed on a 3-T Siemens Tim Trio clinical MRI scanner (Siemens Healthcare, Malvern, Pennsylvania, United States) on patients being treated for low back pain whose disks were categorized into (1) painful and (2) nonpainful subgroups based on provocative diskography and (3) age-matched healthy controls. Painful disks presented both low DHR and T1ρ values, nonpainful disks measured the highest DHR and extended to a higher range of T1ρ, and control disks presented a midrange DHR with the highest T1ρ values. T1ρ MRI evaluated in the NP of IVDs may be useful to establish a threshold (120 milliseconds here) above which indicates a healthy disk, and disks measuring low NP T1ρ (50 to 120 milliseconds here) would require disk height analysis to further categorize the disk. Combining T1ρ MRI and disk height analysis may hold promise in predicting painful disks without provocative diskography, and predictive models should be developed.

T1ρ magnetic resonance imaging quantification of early lumbar intervertebral disc degeneration in healthy young adults.

STUDY DESIGN: Cross-sectional study using T1ρ magnetic resonance imaging (MRI) of lumbar spine in healthy young adults. OBJECTIVE: To evaluate early intervertebral disc degeneration (IDD) quantified by T1ρ- and T2-weighted MRI in asymptomatic young adults and to correlate T1ρ value with Pfirrmann degenerative grade, sex, and body mass index (BMI). SUMMARY OF BACKGROUND DATA: Intervertebral disc starts early to degenerate losing proteoglycan content in the nucleus pulposus (NP). A potential tool for the study of early stage of IDD is T1ρ MRI. T1ρ relaxation time of human discs has been correlated to proteoglycan content in previous studies. METHODS: T1ρ- and T2-weighted images of the lumbar spine were obtained for 63 asymptomatic young subjects (34 men and 29 women; mean age, 22.95 ± 1.8 yr), with a 1.5-T MRI scanner. T1ρ mapping and values in the NP and anulus fibrosus (n = 315) were obtained. Degenerative grade was assessed using T2-weighted images, according to the Pfirrmann scale. Differences in T1ρ value between sexes, BMI, and linear regression analyses with degenerative grade were determined. RESULTS: T1ρ values of NPs were significantly higher than those of anulus fibrosus at all levels. T1ρ values were significantly lower in women at L3-L4 and L4-L5 discs (P < 0.05). T1ρ values decreased linearly with degenerative grade. However, nondegenerated discs (Pfirrmann grades 1 and 2) showed a wide range of T1ρ relaxation time. No significant correlation was observed between T1ρ value and BMI. CONCLUSION: The data of this study showed a significant difference in IDD onset between sexes. T1ρ values correlate with Pfirrmann degenerative grade in young adults. However, the wide distribution of T1ρ values in healthy intervertebral disc highlights the low sensitivity of Pfirrmann grade to detect the early IDD changes. T1ρ can be potentially used as a clinical tool to identify early IDD and to create a reliable quantitative scale.

Quantitative cartilage degeneration associated with spontaneous osteoarthritis in a guinea pig model.

PURPOSE: To determine (i) the feasibility and intra- and inter-scan reproducibility of T(1ρ) MRI in assessing cartilage degeneration in a guinea pig model with naturally occurring joint disease that closely mimics human osteoarthritis (OA), (ii) demonstrate the sensitivity of T(1ρ) MRI in assessing the age dependent cartilage degeneration in OA progression as compared to histopathological changes. MATERIALS AND METHODS: Duncan-Hartley guinea pigs were obtained at various ages and maintained under an IACUC approved protocol. The left hind stifle joint was imaged using T(1ρ) MRI on a 9.4 Tesla Varian horizontal 20 cm bore scanner using a custom surface coil. Reproducibility of T(1ρ) MRI was assessed using 4-month-old guinea pigs (N = 3). Three age cohorts; 3 month (N = 8), 5 month (N = 6), and 9 month (N = 5), were used to determine the age-dependent osteoarthritic changes as measured by T(1ρ) MRI. Validation of age-dependent cartilage degeneration was confirmed by histology and Safranin-O staining. RESULTS: T(1ρ) values obtained in the cartilage of the stifle joint in guinea pigs were highly reproducible with an inter-scan mean coefficient of variation (CV) of 6.57% and a maximum intra-scan CV of 9.29%. Mean cartilage T(1ρ) values in animals with late stage cartilage degeneration were 56.3-56.9 ms (5-9 month cohorts) were both significantly (P < 0.01) higher than that obtained from 3-month-old cohort (44 ms) demonstrating an age-dependent variation. T(1ρ) was shown to be significantly greater than T(2) . T(1ρ) dispersion was observed in this animal model for the first time showing an increase of 45% between 500 Hz and 1500 Hz spin-locking frequency. Cartilage thickness measurements were calculated from single mid-coronal histology sections from same animals used for T(1ρ) MRI. Thickness calculations showed insignificant differences between 3- and 5-month cohorts and was significantly decreased by 9 months of age (P < 0.01). A moderate correlation (R(2) = 0.45) existed between T(1ρ) values and signal intensity of Safranin-O stain. CONCLUSION: The data presented demonstrate that T(1ρ) MRI is highly reproducible in this spontaneous model of OA and may serve as a noninvasive tool to characterize joint cartilage degeneration during OA. Age-dependent changes, verified with histological measurements of proteoglycan loss, correlated with T(1ρ) across different age groups. T(1ρ) has adequate dynamic range and is sensitive to detect and track the progression of cartilage degeneration in the guinea pig model before gross anatomical changes such as cartilage thinning has occurred. This study presents a technological advancement that would permit longitudinal studies of evaluating disease-modifying therapies useful for treating human OA.

T1ρ magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain.

STUDY DESIGN: Prospective magnetic resonance imaging (MRI) study of patients low back pain (LBP) requiring discography as part of their routine clinical diagnoses and asymptomatic age-matched volunteers. OBJECTIVE: To determine whether T1ρ MRI and discography opening pressure (OP) are quantitative biomarkers of disc degeneration in LBP patients and in asymptomatic volunteers. SUMMARY OF BACKGROUND DATA: Disc degenerative disease, a common cause of LBP, is related to the patient's prognosis and serves as a target for therapeutic interventions. However, there are few quantitative measures in the clinical setting. Discography OP and T1ρ MRI are potential biomarkers of disc degenerative disease related to biochemical composition of the intervertebral disc. METHODS: The institutional review board approved all experiments, and informed consent was provided by each subject. Patients being treated for LBP (n = 17; 68 levels; mean age, 44 ± 6 years; and range, 30-53) and control subjects (n = 11; 44 levels; mean age, 43 ± 17 years; and range, 22-76) underwent T1ρ and T2 MRI on a Siemens 3T Tim Trio clinical scanner (Siemens Medical Solutions, Malvern, PA). The LBP patients also received multilevel provocative discography before their MRI. OP was recorded as the pressure when fluid first enters the nucleus of the intervertebral disc. RESULTS: T1ρ was significantly lower in the painful discs (55.3 ± 3.0 ms, mean ± SE) from control (92.0 ± 4.9 ms, P < 0.001) and nonpainful discs (83.6 ± 3.2 ms, P < 0.001). Mean OP for the painful discs (11.8 ± 1.0 psi, mean ± SE) was significantly lower than that for nonpainful discs (19.1 ± 0.7 psi, P < 0.001). Both T1ρ and OP correlated moderately with Pfirrmann degenerative grade. Receiver-operating-characteristic area under the curve was 0.91 for T1ρ MRI and 0.84 for OP for predicting painful discs. CONCLUSION: T1ρ and OP are quantitative measures of degeneration that are consistent across both control subjects and LBP patients. A significant and strong correlation exists between T1ρ values and in vivo OP measurements obtained by discography in LBP patients.